The proposed work is a multifaceted series of studies directed at the relation between activity in primary afferent fibers of small diameter and neural mechanisms associated with (a) nociception, (b) the sensory concomitants of pain and (c) reflex reactions initiated by noxious stimulation. The experimental program is an evolution of past efforts which have led to each of the points of departure. The experiments are to be done on animal models (monkey, cat, rabbit) chosen for their appropriateness to particular questions. One set of experiments focusses on the relation between functional characteristics of primary sensory units with fine (A lambda and C) fibers and the spinal termination regions of the central processes of these afferent fibers; additional evidence on the functional significance of the spinal posteromarginal zone (Lamina I) and the substantia gelatinosa (Lamina II) is sought for the arrangements postulated on the basis of the project's earlier work. A second group of experiments is aimed at the connectivity of Lamina I and II neurons identified by functional input to other neurons of the spinal cord (including those concerned with the flexor reflex) and to higher centers. A third group of experiments relates to the effects of specific intermediary chemical agents and efferent sympathetic stimulation on the enhanced responsiveness and background discharge of the C-fiber cutaneous polymodal nociceptors. The approaches to the work on the central nervous system will utilize intracellular recordings from single neurons, classified by response to various afferent stimulation, and the iontophoretic labelling of these neurons with tracer substances to define their geometry and terminations. Three-dimensional computer graphic analyses will aid in the reconstruction of neuronal relations. The sensory receptor studies will be done using single C fiber recording in preparations permitting control of the circulation and artificial perfusion of the skin.